1.Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes.
Shuo ZHANG ; Hong-Jin LI ; Chun-Mei YANG ; Liu LIU ; Xiao-Ying SUN ; Jiao WANG ; Si-Ting CHEN ; Yi LU ; Man-Qi HU ; Ge YAN ; Ya-Qiong ZHOU ; Xiao MIAO ; Xin LI ; Bin LI
Chinese journal of integrative medicine 2024;30(3):222-229
		                        		
		                        			OBJECTIVE:
		                        			To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective.
		                        		
		                        			METHODS:
		                        			Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ+TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction.
		                        		
		                        			RESULTS:
		                        			TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45+ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01).
		                        		
		                        			CONCLUSIONS
		                        			TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
		                        		
		                        		
		                        		
		                        			Male
		                        			;
		                        		
		                        			Animals
		                        			;
		                        		
		                        			Mice
		                        			;
		                        		
		                        			Tripterygium
		                        			;
		                        		
		                        			Psoriasis/drug therapy*
		                        			;
		                        		
		                        			Keratinocytes
		                        			;
		                        		
		                        			Skin Diseases/metabolism*
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		                        			Cytokines/metabolism*
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		                        			Imiquimod/metabolism*
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		                        			Dermatitis/pathology*
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		                        			Disease Models, Animal
		                        			;
		                        		
		                        			Mice, Inbred BALB C
		                        			;
		                        		
		                        			Skin/metabolism*
		                        			
		                        		
		                        	
2.The relationship between activities of daily living and mental health in community elderly people and the mediating role of sleep quality
Heng-Yi ZHOU ; Jing LI ; Dan-Hua DAI ; Yang LI ; Bin ZHANG ; Rong DU ; Rui-Long WU ; Jia-Yan JIANG ; Yuan-Man WEI ; Jing-Rong GAO ; Qi ZHAO
Fudan University Journal of Medical Sciences 2024;51(2):143-150
		                        		
		                        			
		                        			Objective To explore the relationship and internal path between activities of daily living(ADL),sleep quality and mental health of community elderly people in Shanghai.Methods A questionnaire survey was conducted among community residents aged 60 years and older seeing doctors in community health care center of five streets in Shanghai during Sept to Dec,2021 using convenience sampling.Activities of Daily Living(ADL),Pittsburgh Sleep Quality Index(PSQI)and 10-item Kessler Psychological Distress Scale(K10)were adopted in the survey.Single factor analysis,correlation analysis and multiple linear regression were used to analyze the data.The effect relationship between the variables was tested using Bootstrap's mediated effects test.Results A total of 1 864 participants were included in the study.The average score was 15.53±4.47 for ADL,5.60±3.71 for PSQI and 15.50±6.28 for K10.The rate of ADL impairment,poor sleep quality,poor and very poor mental health of the elderly were 23.6%,27.3%,11.9%and 4.9%,respectively.ADL and sleep quality were all positively correlated with mental health(r=0.321,P<0.001;r=0.466,P<0.001);ADL was positively correlated with sleep quality(r=0.294,P<0.001).Multiple linear results of factors influencing mental health showed that ADL(β= 0.457,95%CI:0.341-0.573),sleep quality(β =0.667,95%CI:0.598-0.737)and mental health were positively correlated(P<0.001).Sleep quality partially mediated the relationship between ADL and mental health(95%CI:0.078-0.124)with an effect size of 33.0%.Conclusion Sleep quality is a mediator between ADL and mental health among community elderly people.Improving ADL and sleep quality may improve mental health in the population.
		                        		
		                        		
		                        		
		                        	
3.Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine (version 2024)
Xiao CHEN ; Hao ZHANG ; Man WANG ; Guangchao WANG ; Jin CUI ; Wencai ZHANG ; Fengjin ZHOU ; Qiang YANG ; Guohui LIU ; Zhongmin SHI ; Lili YANG ; Zhiwei WANG ; Guixin SUN ; Biao CHENG ; Ming CAI ; Haodong LIN ; Hongxing SHEN ; Hao SHEN ; Yunfei ZHANG ; Fuxin WEI ; Feng NIU ; Chao FANG ; Huiwen CHEN ; Shaojun SONG ; Yong WANG ; Jun LIN ; Yuhai MA ; Wei CHEN ; Nan CHEN ; Zhiyong HOU ; Xin WANG ; Aiyuan WANG ; Zhen GENG ; Kainan LI ; Dongliang WANG ; Fanfu FANG ; Jiacan SU
Chinese Journal of Trauma 2024;40(3):193-205
		                        		
		                        			
		                        			Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.
		                        		
		                        		
		                        		
		                        	
4.National bloodstream infection bacterial resistance surveillance report (2022) : Gram-negative bacteria
Zhiying LIU ; Yunbo CHEN ; Jinru JI ; Chaoqun YING ; Qing YANG ; Haishen KONG ; Haifeng MAO ; Hui DING ; Pengpeng TIAN ; Jiangqin SONG ; Yongyun LIU ; Jiliang WANG ; Yan JIN ; Yuanyuan DAI ; Yizheng ZHOU ; Yan GENG ; Fenghong CHEN ; Lu WANG ; Yanyan LI ; Dan LIU ; Peng ZHANG ; Junmin CAO ; Xiaoyan LI ; Dijing SONG ; Xinhua QIANG ; Yanhong LI ; Qiuying ZHANG ; Guolin LIAO ; Ying HUANG ; Baohua ZHANG ; Liang GUO ; Aiyun LI ; Haiquan KANG ; Donghong HUANG ; Sijin MAN ; Zhuo LI ; Youdong YIN ; Kunpeng LIANG ; Haixin DONG ; Donghua LIU ; Hongyun XU ; Yinqiao DONG ; Rong XU ; Lin ZHENG ; Shuyan HU ; Jian LI ; Qiang LIU ; Liang LUAN ; Jilu SHEN ; Lixia ZHANG ; Bo QUAN ; Xiaoping YAN ; Xiaoyan QI ; Dengyan QIAO ; Weiping LIU ; Xiusan XIA ; Ling MENG ; Jinhua LIANG ; Ping SHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2024;17(1):42-57
		                        		
		                        			
		                        			Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System(BRICS)were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute(CLSI). WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period,9 035 strains of Gram-negative bacteria were collected from 51 hospitals,of which 7 895(87.4%)were Enterobacteriaceae and 1 140(12.6%)were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli( n=4 510,49.9%), Klebsiella pneumoniae( n=2 340,25.9%), Pseudomonas aeruginosa( n=534,5.9%), Acinetobacter baumannii complex( n=405,4.5%)and Enterobacter cloacae( n=327,3.6%). The ESBLs-producing rates in Escherichia coli, Klebsiella pneumoniae and Proteus spp. were 47.1%(2 095/4 452),21.0%(427/2 033)and 41.1%(58/141),respectively. The prevalence of carbapenem-resistant Escherichia coli(CREC)and carbapenem-resistant Klebsiella pneumoniae(CRKP)were 1.3%(58/4 510)and 13.1%(307/2 340);62.1%(36/58)and 9.8%(30/307)of CREC and CRKP were resistant to ceftazidime/avibactam combination,respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)complex was 59.5%(241/405),while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa(CRPA)was 18.4%(98/534). There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions,with statistically significant differences in the prevalence of CRKP and CRPA( χ2=20.489 and 20.252, P<0.001). The prevalence of CREC,CRKP,CRPA,CRAB,ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals( χ2=11.953,81.183,10.404,5.915,12.415 and 6.459, P<0.01 or <0.05),while the prevalence of CRPA was higher in economically developed regions(per capita GDP ≥ 92 059 Yuan)than that in economically less-developed regions(per capita GDP <92 059 Yuan)( χ2=6.240, P=0.012). Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend,and Escherichia coli is ranked in the top,while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different,and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.
		                        		
		                        		
		                        		
		                        	
5.Establishment of HPLC characteristic chromatogram and quantitative transmission laws for Baqi Rougan Decoction reference sample
Sai-Long GENG ; Qin ZHOU ; Shui-Gen SUN ; Man LI ; Li-Jie ZHAO ; Ji-Quan ZHANG ; Yi FENG
Chinese Traditional Patent Medicine 2024;46(2):370-378
		                        		
		                        			
		                        			AIM To establish the HPLC characteristic chromatogram of Baqi Rougan Decoction reference sample,and to investigate its quantitative transmission laws.METHODS The contents of calycosin 7-O-glucoside,hesperidin,rosmarinic acid,curcumenol and nystose were determined.The transfer rates of decoction piece-aqueous decoction-reference sample were calculated,after which the paste-forming rate and pH value were recorded.RESULTS There were sixteen characteristic peaks in fifteen batches of reference samples with the similarities of 0.90,nine of which were identified.The average transfer rates of nystose and calycosin 7-O-glucoside in the reference sample were(83.14±6.25)%and(77.81±8.31)%,while those of rosmarinic acid and curcumenol in the aqueous decoction-reference sample were(81.71±6.27)%and(72.16±5.91)%,along with the average paste-forming rate and pH value of(38.91%±1.46%)and 5.13±0.08,respectively.CONCLUSION This stable and feasible method can provide a reference for the selection of preparation process and evaluation of key chemical properties for Baqi Rougan Decoction.
		                        		
		                        		
		                        		
		                        	
6.Clinicopathological study of 24 cases of monkeypox virus infection-related rashes
Yanhua PANG ; Xingang ZHOU ; Man LI ; Xiangmei CHEN ; Liang ZHANG ; Kun YANG ; Ting LIU ; Jiamin CHEN ; Simeng LIU ; Weimin TONG ; Jiangyang LU ; Peng WANG
Chinese Journal of Pathology 2024;53(10):1011-1017
		                        		
		                        			
		                        			Objective:To investigate the clinicopathological characteristics of rashes in monkeypox patients through a series of skin biopsies, and examine their pathological features and the most effective tests.Methods:Patients with monkeypox virus infection admitted to Beijing Ditan Hospital from June to August 2023 were identified. Among them, 24 patients underwent skin biopsies for clinical pathological study that were included in this study. Clinical information, rash pictures, and nucleic acid test results were analyzed using histopathology, immunohistochemistry, RNAscope ? hybridization and electron microscopy. Results:All 24 patients were male, including 14 patients with concurrent human immunodeficiency virus infection. Their average age was (32.3±5.4) years. The nucleic acid test confirmed monkeypox virus infection. The clinical feature of monkeypox rashes was solitary rather than clustered distribution, with rashes occurring in similar phase, distinguishing it from herpesvirus. The rashes in these patients were mostly scattered, with an average of (13.0±11.8) rashes, and most commonly present in the perineum, face, limbs, and trunk. The three main pathological features of these rashes were ballooning degeneration of the epidermal spinous cell layer, the characteristic intra-cytoplasmic Guarnieri′s bodies and significant infiltration of inflammatory cells in whole dermal layer. Immunohistochemistry, RNAscope ? hybridization, and electron microscopy can all effectively detect the monkeypox virus. Electron microscopy showed viral replication in various types of skin cells. Conclusions:The study describes the pathological features of monkeypox virus rashes. Pathological examination of skin biopsy samples is helpful to diagnose these rashes. The study suggests that the monkeypox virus has a unique epitheliotropic affinity and can infect various types of cells in the skin.
		                        		
		                        		
		                        		
		                        	
7.Traditional Chinese Medicine Syndrome Element, Evolutionary Patterns of Patients with Hepatitis B Virus-Related Acute on Chronic Liver Failure at Different Stages: A Multi-Center Clinical Study
Simiao YU ; Kewei SUN ; Zhengang ZHANG ; Hanmin LI ; Xiuhui LI ; Hongzhi YANG ; Qin LI ; Lin WANG ; Xiaozhou ZHOU ; Dewen MAO ; Jianchun GUO ; Yunhui ZHUO ; Xianbo WANG ; Xin DENG ; Jiefei WANG ; Wukui CAO ; Shuqin ZHANG ; Mingxiang ZHANG ; Jun LI ; Man GONG ; Chao ZHOU
Journal of Traditional Chinese Medicine 2024;65(12):1262-1268
		                        		
		                        			
		                        			ObjectiveTo explore the syndrome elements and evolving patterns of patients with hepatitis B virus-related acute on chronic liver failure (HBV-ACLF) at different stages. MethodsClinical information of 1,058 hospitalized HBV-ACLF patients, including 618 in the early stage, 355 in the middle stage, and 85 in the late stage, were collected from 18 clinical centers across 12 regions nationwide from January 1, 2012 to February 28, 2015. The “Hepatitis B-related Chronic and Acute Liver Failure Chinese Medicine Clinical Questionnaire” were designed to investigate the basic information of the patients, like the four diagnostic information (including symptoms, tongue, pulse) of traditional Chinese medicine (TCM), and to count the frequency of the appearance of the four diagnostic information. Factor analysis and cluster analysis were employed to determine and statistically analyze the syndrome elements and patterns of HBV-ACLF patients at different stages. ResultsThere were 76 four diagnostic information from 1058 HBV-ACLF patients, and 53 four diagnostic information with a frequency of occurrence ≥ 5% were used as factor analysis entries, including 36 symptom information, 12 tongue information, and 5 pulse information. Four types of TCM patterns were identified in HBV-ACLF, which were liver-gallbladder damp-heat pattern, qi deficiency and blood stasis pattern, liver-kidney yin deficiency pattern, and spleen-kidney yang-deficiency pattern. In the early stage, heat (39.4%, 359/912) and dampness (27.5%, 251/912) were most common, and the pattern of the disease was dominated by liver-gallbladder damp-heat pattern (74.6%, 461/618); in the middle stage, dampness (30.2%, 187/619) and blood stasis (20.7%, 128/619) were most common, and the patterns of the disease were dominated by liver-gallbladder damp-heat pattern (53.2%, 189/355), and qi deficiency and blood stasis pattern (27.6%, 98/355); and in the late stage, the pattern of the disease was dominated by qi deficiency (26.3%, 40/152) and yin deficiency (20.4%, 31/152), and the patterns were dominated by qi deficiency and blood stasis pattern (36.5%, 31/85), and liver-gallbladder damp-heat pattern (25.9%, 22/85). ConclusionThere are significant differences in the distribution of syndrome elements and patterns at different stages of HBV-ACLF, presenting an overall trend of evolving patterns as "from excess to deficiency, transforming from excess to deficiency", which is damp-heat → blood stasis → qi-blood yin-yang deficiency. 
		                        		
		                        		
		                        		
		                        	
		                				8.Two new isocoumarins from cave-derived Metarhizium anisopliae  NHC-M3-2
		                			
		                			Rong-xiang WU ; Jie-lan GUO ; Hua HUANG ; Jing-jing LIAO ; Yi HAO ; Fan-dong KONG ; Li-man ZHOU ; Chao-jun ZHANG
Acta Pharmaceutica Sinica 2024;59(9):2588-2593
		                        		
		                        			
		                        			 Extracting extracts of secondary metabolites from the karst cave fungus 
		                        		
		                        	
9.Comparative analysis of maxillary distraction osteogenesis and Le Fort Ⅰ osteotomy on maxillary hypoplasia in patients with complex cleft lip and palate
Tianci ZHANG ; Huanzhuo ZHAO ; Man JIANG ; Tao WANG ; Jianping ZHOU ; Li CAO ; Leilei ZHENG
Chinese Journal of Plastic Surgery 2024;40(8):846-856
		                        		
		                        			
		                        			Objective:To compare the efficacy of maxillary distraction osteogenesis (DO) and Le FortⅠ osteotomy (LFⅠ) in patients with complex cleft lip and palate.Methods:A retrospective study was conducted, clinical data were collected involving patients with complex cleft lip and palate who required combined orthodontic and orthognathic treatment and were treated at the Stomatological Hospital of Chongqing Medical University from January 2015 to December 2022. Patients were divided into three groups based on the surgical method used for the maxilla: total maxillary distraction (TMD, group A), anterior maxillary distraction (AMD, group B), and Le Fort Ⅰ osteotomy (LFⅠ, group C). Cone-beam CT scans and lateral cephalograms were obtained preoperatively and at 3 months postoperatively. Three-dimensional reconstructions were performed using Mimics 21.0 and Dolphin Imaging 11.9 software to evaluate changes in craniofacial morphology and airway. Data analysis was conducted using SPSS 25.0. Intragroup comparisons before and after surgery were performed using the Wilcoxon rank sum test, and intergroup comparisons among the three groups were conducted using the Kruskal-Wallis H test. Results:A total of 15 patients were included, with 5 patients in each group. The cohort comprised 8 males and 7 females, aged between 15 and 21 years. There were no statistically significant differences in the distribution of gender, age, or cleft lip and palate classification among the three groups ( P>0.05). Postoperatively, all three groups showed improvement in maxillary hypoplasia. Compared to preoperative measurements, the angle formed by the points A (subspinale), N (nasion), and B (supramentale) (ANB angle) increased in all three groups (all P<0.05). The vertical distance from point A to the nasion perpendicular (A-Nperp) increased in groups A and B ( P<0.05 for both) but not in group C ( P>0.05). The area of the alveolar gap showed an increasing trend in all three groups ( P>0.05). The mandibular plane angle (FMA) decreased postoperatively in group B but showed an increasing trend in the other two groups, though the differences were not statistically significant ( P>0.05). Postoperative airway volume increased or showed an increasing trend in groups A ( P<0.05) and B ( P>0.05) but decreased in group C ( P>0.05). Intergroup comparisons showed significant differences in the angle formed by the sella (S), nasion (N), and point A (SNA angle) and the vertical distance from the anterior nasal spine to the coronal plane (ANS-CP) ( P<0.05). Group A had significantly larger SNA angles and ANS-CP values than group B, and the ANS-CP value in group A was significantly larger than in group C (all P<0.05). There were no other statistically significant differences among the groups ( P>0.05). Conclusion:For patients with severe maxillary hypoplasia due to complex cleft lip and palate, TMD can correct sagittal discrepancies between the upper and lower jaws, increase upper airway volume, but may potentially enlarge the alveolar gap area and increase vertical height of the maxilla. AMD result in less change in maxillary position compared to TMD and is mainly used for patients with severe maxillary dental crowding, needing increased arch length, having minor sagittal discrepancies, or with preexisting velopharyngeal dysfunction. LFⅠ result in changes in maxillary position similar to AMD but less than TMD, making it suitable for patients with moderate maxillary hypoplasia and mild maxillary dental crowding. The advantage of LFⅠ lies in its precise postoperative occlusal design and accurate three-dimensional movement of the jaw.
		                        		
		                        		
		                        		
		                        	
10.Anesthetic effects of percutaneous nephrolithotomy for upper urinary calculi under two-plane local anesthesia
Jianpo ZHAI ; Ning ZHOU ; Hai WANG ; Guizhong LI ; Libo MAN
Journal of Modern Urology 2024;29(12):1051-1054
		                        		
		                        			
		                        			[Objective] To Compare the effectiveness of conventional local anesthesia (CLA) and two-plane local anesthesia (TPLA) in percutaneous nephrolithotomy (PCNL) so as to provide reference for clinical selection of appropriate anesthetic methods. [Methods] Clinical data of 345 patients with renal or ureteral calculi who underwent PCNL under local infiltration anesthesia in our hospital during Jan.2013 and Dec.2023 were retrospectively analyzed.The patients were divided into CLA group (n=114) and TPLA group (n=231) according to anesthetic methods.The intraoperative visual analogue scale (VAS) score, stone-free rate and incidence of complications were compared between the two groups. [Results] There were no significant differences in the baseline data between the two groups (P>0.05). When the cutaneous and renal channels were established, the VAS score was lower in the TPLA group than in the CLA group [(3.2±0.5) vs. (3.8±0.4), P=0.023]. However, there was no significant difference in the VAS score during lithotripsy [(3.3±0.5) vs. (3.4±0.5), P=0.061]. There were no significant differences between the two groups in terms of operation time, stone-free rate, hemoglobin drop, postoperative hospital stay, and time to remove nephrostomy tube and DJ tube retention time (P>0.05). [Conclusion] Both CLA and TPLA can provide good analgesia in PCNL, but TPLA can significantly reduce the pain sensation when the cutaneous and renal channels are established.
		                        		
		                        		
		                        		
		                        	
            
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